Background: Anti-PD1/PD-L1-directed immune checkpoint inhibitors (ICI) are game changers in advanced non-small-cell lung cancer (NSCLC), but biomarkers are lacking. The aim of our study was to find clinically relevant biomarkers of the efficacy of ICI in non-squamous NSCLC.
Methods:We conducted a retrospective study of patients receiving ICI for advanced non squamous NSCLC in two cohorts. For a subset of patients, RNAseq data were generated on tumor biopsy taken before ICI. The primary end point was progressionfree survival (PFS) under ICI. Secondary end point was overall survival (OS) from ICI initiation.Results: In our cohort, we studied 231 patients. Clinical characteristics included KRAS mutant status (n¼88), TTF1-positive expression (n¼136), LIPI (Lung Immune Prognostic Index) score of 0 (n¼116). In the training set, by multivariate Cox analysis, lack of TTF1 expression, LIPI score>0, line of treatment>1, and presence of liver metastases were associated with poorer PFS, while WHO performance status, lack of TTF1 expression, LIPI score>0, line of treatment>1, and presence of liver or bone metastases were associated with poorer OS. TTF1 and PD-L1 status could be used to stratify PFS and OS and improve the AUC for prediction of prognosis in comparison with the PD-L1 gold standard. Using an external validation cohort of 154 patients treated with ICI for non-squamous NSCLC, we confirmed the independent prognostic role of TTF1. Similarly, use of TTF1 with PD-L1 status could be used to stratify PFS and OS and improve the AUC for the prediction of prognosis in comparison to the PD-L1 gold standard.Conclusions: TTF1 expression and PD-L1 can be used to stratify risk and predict PFS and OS in patients treated with ICI for NS-NSCLC.Legal entity responsible for the study: Centre Georges-François Leclerc.
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